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Pancreatic High-Grade Neuroendocrine Neoplasms in the Korean Population: A Multicenter Study

Cancer Research and Treatment 2020년 52권 1호 p.263 ~ 276
김해령 ( Kim Hae-Ryoung ) - Seoul National University Hospital Department of Pathology

안소연 ( An So-Yeon ) - Catholic University College of Medicine Incheon St. Mary’s Hospital Department of Pathology
이경번 ( Lee Kyoung-Bun ) - Seoul National University Hospital Department of Pathology
안상정 ( Ahn Sang-Jeong ) - Catholic Kwandong University College of Medicine International St. Mary’s Hospital Department of Pathology
박도윤 ( Park Do-Youn ) - Saint Maria Pathology Department of Pathology
김조헌 ( Kim Jo-Heon ) - Chonnam National University Medical School Department of Pathology
강동욱 ( Kang Dong-Wook ) - Eulji University Hospital Department of Pathology
 ( Kim Min-Ju ) - Seegen Medical Foundation
장미수 ( Chang Mee-Soo ) - Seoul National University College of Medicine Department of Pathology
정은선 ( Jung Eun-Sun ) - Catholic University College of Medicine Seoul St. Mary’s Hospital Department of Pathology
김준미 ( Kim Joon-Mee ) - Inha University Hospital Department of Pathology
최윤정 ( Choi Yoon-Jung ) - National Health Insurance Service Ilsan Hospital Department of Pathology
진소영 ( Jin So-Young ) - SoonChunHyang University Seoul Hospital Department of Pathology
장희경 ( Chang Hee-Kyung ) - Kosin University Gospel Hospital Department of Pathology
조미원 ( Cho Mee-Yon ) - Yonsei University Wonju College of Medicine Department of Pathology
강윤경 ( Kang Yun-Kyung ) - Inje University Seoul Paik Hospital Department of Pathology
강명희 ( Kang Myung-Hee ) - Gachon University Gil Medical Center Department of Pathology
안수민 ( Ahn Soo-Min ) - Seoul National University College of Medicine Seoul National University Bundang Hospital Department of Pathology
김윤화 ( Kim Youn-Wha ) - Kyung Hee University School of Medicine Department of Pathology
홍승모 ( Hong Seung-Mo ) - University of Ulsan College of Medicine Asan Medical Center Department of Pathology

Abstract


Purpose: The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 PanNETs and PanNECs is difficult in clinical practice.

Materials and Methods: Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs.

Results: Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity.

Conclusion: Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.

키워드

Pancreas; Neuroendocrine tumors; Neuroendocrine carcinoma; Immunohistochemistry
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